Ultraviolet light (UVL)-induced carcinogenesis in mice represents an excellent model to study tumor immunology. The majority of primary neoplasms induced with this physical agent are immunologically rejected when transplanted to normal syngeneic recipients but capable of progressive growth when transplanted to UVL-exposed animals. This observation has been extensively investigated and appears to be due, at least in part, to effects mediated by UVL directly on the immunological apparatus. To date, UVL-induced tumors have mainly served as a tool to study this biological phenomenon.
The aim of our study is to address a number of questions crucial to the development of this model, using a reversal of the tack taken in past investigations. Employing tumor-specific immunity as a tool, we propose: (1) to question the clonal nature of UVL-induced tumors; (2) to question the possibility that tumor-tumor or tumor-somatic cell hybridization may represent an integral component of normal tumor progression; (3) to further analyze the tumorigenic heterogeneity of cells within primary UVL-induced regressor phenotype tumors; (4) to determine whether the gene(s) which encodes for UVL-mediated transformation and the gene(s) which encodes for a particular TSTA are identical or at least linked; and (5) to investigate further the phenomenon that cloned lines derived from UVL-regressor phenotype tumors can be converted with normal splenocytes (induction, selection, or both) to a virulent progressor which expresses a TSTA identical to the original cell line. The facilities and technical expertise needed to conduct these studies are unique in that a basic understanding of contemporary cellular immunology, tumor immunology, photobiology, somatic cell genetics, and molecular genetics is essential. It is obvious that many aspects of experimental photocarcinogenesis have important human implications. UVL represents a well-recognized and documented human carcinogen, and its ability to modify certain human immune responses is just beginning to be appreciated. (M)
Showing the most recent 10 out of 43 publications
